Cell Communications

J. Sam Johnson, M.Sc., M.Pharm., Ph.D.,

 No cell can live in isolation, must interact with
environment

 In multicellular organisms, cells must

communicate with each other

 Growth involves intricate signaling

 Same with Differentiatio n

 Even Metabolism requires signaling

 Earl W. Sutherland, discovered how hormone
epinephrine acts on cells, suggested that
cells receiving signals went t h r o u g h t h r e e
p ro cesses:

◦ Reception of signal

◦ Transduction of signal

◦ Response to signal
 Stages in Cell Signaling
EXTRACELLULAR
FLUID

Reception Transduction CYTOPLASM Response

Plasma membrane
Receptor

Activation
of cellular
response

Relay molecules in a signal transduction

pathway
Signal
molecule
 Cells can detect what's going on around
them, and they can respond in real time to
cues from their neighbors and environment.

 At this very moment, your cells are sending

and receiving millions of messages in the
form of chemical signaling molecules!
 Cells typically communicate using chemical
signals.

 These chemical signals, which are proteins or

other molecules produced by a sending cell, are
often secreted from the cell and released into the
extracellular space.

 Not all cells can “hear” a particular chemical

message.

 In order to detect a signal (that is, to be a target

cell), a neighbor cell must have the right receptor
for that signal.
 When a signaling molecule binds to its receptor, it
alters the shape or activity of the receptor,
triggering a change inside of the cell.

 Signaling molecules are often called ligands.

 The message carried by a ligand is often relayed

through a chain of chemical messengers inside the
cell.

 Ultimately, it leads to a change in the cell, such as

alteration in the activity of a gene or even the
induction of a whole process, such as cell division.

 Thus, the original intercellular (between-cells) signal

is converted into an intracellular (within-cell) signal
that triggers a response.
 Cell-cell signaling involves the transmission of a signal
from a sending cell to a receiving cell.

 However, not all sending and receiving cells are next-

door neighbors, nor do all cell pairs exchange signals
in the same way.

 There are four basic categories of chemical signaling

found in multicellular organisms:

◦ Paracrine signaling,
◦ Autocrine signaling,
◦ Endocrine signaling, and
◦ Signaling by direct contact.

 The main difference between the different categories

of signaling is the distance that the signal travels
through the organism to reach the target cell.
 Often, cells that are near one another
communicate through the release of chemical
messengers (ligands that can diffuse through the
space between the cells).

 This type of signaling, in which cells

communicate over relatively short distances, is
known as paracrine signaling.

 Paracrine signaling allows cells to locally

coordinate activities with their neighbors.
Although they're used in many different tissues
and contexts, paracrine signals are especially
important during development, when they allow
one group of cells to tell a neighboring group of
cells what cellular identity to take on
 One unique example of paracrine signaling
is synaptic signaling, in which nerve cells
transmit signals.

 When the sending neuron fires, an electrical

impulse moves rapidly through the cell, traveling
down a long, fiber-like extension called an axon.

 When the impulse reaches the synapse, it triggers

the release of ligands called neurotransmitters,
which quickly cross the small gap between the
nerve cells.

 When the neurotransmitters arrive at the

receiving cell, they bind to receptors and cause a
chemical change inside of the cell (often, opening
ion channels and changing the electrical potential
across the membrane).
 In autocrine signaling, a cell signals to itself,
releasing a ligand that binds to receptors on its own
surface (or, depending on the type of signal, to
receptors inside of the cell).

 Autocrine signaling is important during development,

helping cells take on and reinforce their correct
identities. From a medical standpoint, autocrine
signaling is important in cancer and is thought to
play a key role in metastasis (the spread of cancer
from its original site to other parts of the body).

 In many cases, a signal may have both autocrine and

paracrine effects, binding to the sending cell as well
as other similar cells in the area.
 When cells need to transmit signals over long
distances, they often use the circulatory system
as a distribution network for the messages they
send.

 In long-distance endocrine signaling, signals are

produced by specialized cells and released into
the bloodstream, which carries them to target
cells in distant parts of the body.

 Signals that are produced in one part of the body

and travel through the circulation to reach far-
away targets are known as hormones.
 Gap junctions in animals and plasmodesmata in
plants are tiny channels that directly connect
neighboring cells.

 These water-filled channels allow small signaling

molecules, called intracellular mediators, to
diffuse between the two cells.

 Small molecules, such as calcium ions are able to

move between cells, but large molecules like
proteins and DNA cannot fit through the
channels without special assistance.
 In another form of direct signaling, two cells
may bind to one another because they carry
complementary proteins on their surfaces.

 When the proteins bind to one another, this

interaction changes the shape of one or both
proteins, transmitting a signal.

 This kind of signaling is especially important

in the immune system, where immune cells
use cell-surface markers to recognize “self”
cells (the body's own cells) and cells infected
by pathogens.
 A cell junction (or intercellular bridge) is a type of
structure that exists within the tissue of
some multicellular organisms, such as animals.

 Cell junctions consist of multiprotein

complexes that provide contact between
neighboring cells or between a cell and
the extracellular matrix.

 They also build up the paracellular barrier of

epithelia and control the paracellular transport.

 Cell junctions are especially abundant

in epithelial tissues.
 Cell junctions are especially important in
enabling communication between
neighboring cells via specialized proteins
called communicating junctions.

 Cell junctions are also important in reducing

stress placed upon cells.

 Combined with cell adhesion

molecules and extracellular matrix, cell
junctions help hold animal cells together.
 In vertebrates, there are three major types of
cell junction:

◦ Adherens junctions, desmosomes and

hemidesmosomes (anchoring junctions)
◦ Gap junctions (communicating junction)
◦ Tight junctions (occluding junctions)
 Adherens Junction - joins actin bundles
between cells.

 Desmosome - joins intermediate filaments

between cells.

 Hemi-desmosome - anchors cell

intermediate filaments to ECM

 Gap Junction - cell-cell communication

(signaling), passage of small molecules.

 Tight Junction - seals neighbouring cells.

 The chains of molecules that relay signals
inside a cell are known as intracellular signal
transduction pathways.

 When a ligand binds to a cell-surface

receptor, the receptor’s intracellular domain
(part inside the cell) changes in some way.

 Generally, it takes on a new shape, which may

make it active as an enzyme or let it bind
other molecules.
 The change in the receptor sets off a series of
signaling events.

 For instance, the receptor may turn on

another signaling molecule inside of the cell,
which in turn activates its own target.

 This chain reaction can eventually lead to a

change in the cell's behavior or
characteristics.
 Proteins can be activated or inactivated in a
variety of ways.

 However, one of the most common tricks for

altering protein activity is the addition of a
phosphate group to one or more sites on the
protein, a process called phosphorylation.

 In general, phosphorylation isn’t permanent. To

flip proteins back into their non-phosphorylated
state, cells have enzymes called phosphatases,
which remove a phosphate group from their
targets.
 Although proteins are important in signal
transduction pathways, other types of molecules
can participate as well.

 Many pathways involve second messengers,

small, non-protein molecules that pass along a
signal initiated by the binding of a ligand (the
“first messenger”) to its receptor.

 Second messengers include

◦ Ca2+ ions
◦ Cyclic AMP (cAMP), a derivative of ATP
◦ Inositol phosphates, which are made from
phospholipids.
 Signaling pathways share a common goal: to
produce some kind of cellular response.

◦ Gene Expression
◦ Growth
◦ Cellular Metabolism
◦ Apoptosis